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A single-nucleus transcriptomic atlas of primate liver aging uncovers the pro-senescence role of SREBP2 in hepatocytes

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Protein & Cell 2024年第2期15卷 98-120页

作者： Shanshan Yang Chengyu Liu Mengmeng Jiang Xiaoqian Liu Lingling Geng Yiyuan Zhang shuhui Sun Kang Wang jian Yin Shuai Ma Si Wang Juan Carlos Izpisua Belmonte Weiqi Zhang Jing Qu Guang-Hui Liu Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders Xuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China Xuanwu Hospital Capital Medical University Beijing 100053China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China Aging Biomarker Consortium Beijing 100101China Altos Labs Inc.San DiegoCA 94022USA

Aging increases the risk ofliver diseases and systemic susceptibility to aging-related diseases.However,cell type-specific changes and the underlying mechanism of liver aging in higher vertebrates remain incompletely characterized.Here,we constructed the first single-nucleus transcriptomic landscape of primate liver aging,in which we resolved cell type-specific gene expression fluctuation in hepatocytes across three liver zonations and detected aberrant cell-cell interactions between hepatocytes and niche cells.Upon in-depth dissection of this rich dataset,we identifed impaired lipid metabolism and upregulation of chronic inflammation-related genes prominently associated with declined liver functions during aging.In particular,hyperactivated sterol regulatory element-binding protein(SREBP)signaling was a hallmark of the aged liver,and consequently,forced activation of SREBP2 in human primary hepatocytes recapitulated in vivo aging phenotypes,manifesting as impaired detoxification and accelerated cellular senescence.This study expands our knowledge of primate liver aging and informs the development of diagnostics and therapeutic interventions for liver aging and associated diseases.

关键词： single-nucleus RNA sequencing liver hepatocytes aging senescence SREBP2

A novel order-reduced thermal-coupling electrochemical model for lithium-ion batteries

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Chinese Physics B 2024年第5期33卷 637-654页

作者：谢奕展王舒慧王震坡程夕明 School of Mechanical Engineering Beijing Institute of TechnologyBeijing 100081China National Engineering Research Center for Electric Vehicles Beijing Institute of TechnologyBeijing 100081China The Hong Kong University of Science and Technology (Guangzhou) Sustainable Energy and Environment Thrust and Guangzhou MunicipalKey Laboratory of Materials InformaticsGuangzhou 511400China

Although the single-particle model enhanced with electrolyte dynamics(SPMe)is simplified from the pseudo-twodimensional(P2D)electrochemical model for lithium-ion batteries,it is difficult to solve the partial differential equations of solid–liquid phases in real-time applications.Moreover,working temperatures have a heavy impact on the battery behavior.Hence,a thermal-coupling SPMe is constructed.Herein,a lumped thermal model is established to estimate battery temperatures.The order of the SPMe model is reduced by using both transfer functions and truncation techniques and merged with Arrhenius equations for thermal effects.The polarization voltage drop is then modified through the use of test data because its original model is unreliable theoretically.Finally,the coupling-model parameters are extracted using genetic algorithms.Experimental results demonstrate that the proposed model produces average errors of about 42 mV under 15 constant current conditions and 15 mV under nine dynamic conditions,respectively.This new electrochemicalthermal coupling model is reliable and expected to be used for onboard applications.

关键词： lithium-ion batteries order-reduced electrochemical models SPMe thermal-coupling model transient polarization voltage drop

上海音乐学院民族音乐研究室成立70周年感怀

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人民音乐 2024年第1期 57-62页

作者：郭树荟上海音乐学院音乐学系

上海音乐学院民族音乐研究室自1953年成立,迄今已有70年的历史。1953年,贺绿汀为了最大限度地体现其教学思想与教学理念,身先士卒、身体力行并首任民族音乐研究室主任,作为专业高等院校率先开拓“向民间音乐学习”,是“民间艺术进校园... 详细信息

上海音乐学院民族音乐研究室自1953年成立,迄今已有70年的历史。1953年,贺绿汀为了最大限度地体现其教学思想与教学理念,身先士卒、身体力行并首任民族音乐研究室主任,作为专业高等院校率先开拓“向民间音乐学习”,是“民间艺术进校园进课堂”的倡导者。贺老为民族音乐研究室制定了非常具体的个案研究、教学实践、教材撰写以及创作参与的多样性民族音乐在高校传承的实施细则方案与宗旨。从民族音乐研究室到民族音乐课,从收集整理到课堂教学及教材的形成,70年来的理论与实践、教学与科研,民族音乐研究室为中国民族民间音乐在通向专业教育的历程中,在历经了漫长而充满曲折的教学与科研的实践中,为中国音乐的发展树立了风范与学术标杆。

关键词：教学与科研上海音乐学院理论与实践实施细则贺绿汀课堂教学教学思想教学理念

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数字时代隐私权保护的立法因应

法学 2024年第3期 17-31页

作者：李姝卉西北政法大学法治学院

数字技术在为人类生活带来便利、促进数字经济发展和数字服务能力及效率提升的同时,使自然人隐私权面临以保障安全和发展经济为名的潜在威胁、数字伦理缺失等多重消解风险。当下中国形成了以《数据安全法》保障数据安全、以《个人信息... 详细信息

数字技术在为人类生活带来便利、促进数字经济发展和数字服务能力及效率提升的同时,使自然人隐私权面临以保障安全和发展经济为名的潜在威胁、数字伦理缺失等多重消解风险。当下中国形成了以《数据安全法》保障数据安全、以《个人信息保护法》规制个人信息处理活动、以《民法典》保护自然人隐私权的立法模式。但在数字时代,上述立法模式存在对个人信息和隐私界定不明、缺少流动场景下对隐私权社会属性的重视、隐私权法律救济和责任规制缺失、国内外的隐私权保护立法衔接不足等问题。在数字时代,我国对隐私权保护立法的完善,应从法理和适用规则上界分隐私和个人信息,依群体分类保护隐私权,完善私密信息的法律救济规则,健全对重点场景和行业的法律责任追究机制,建立公平公正的数字贸易与隐私权保护国际规则,强化自然人对数字社会治理的参与等。

关键词：数字时代隐私个人信息私密信息隐私权保护

Id2 epigenetically controls CD8^(+)T-cell exhaustion by disrupting the assembly of the Tcf3-LSD1 complex

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Cellular & Molecular Immunology 2024年第3期21卷 292-308页

作者： Yiming Li Mingwei Han Haolin Wei Wan Huang Zhinan Chen Tianjiao Zhang Meirui Qian Lin Jing Gang Nan Xiuxuan Sun shuhui Dai Kun Wang Jianli Jiang Ping Zhu Liang Chen Department of Cell Biology of National Translational Science Center for Molecular Medicine and Department of Clinical Immunology of Xijing Hospital Fourth Military Medical UniversityXi’anShaanxi 710032China State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases GanzhouJiangxi341000Xi’anShaanxi 710032China School of Medicine Shanghai UniversityShanghai 200444China

CD8^(+)T-cell exhaustion is a state of dysfunction that promotes tumor progression and is marked by the generation of Slamf6^(+)progenitor exhausted(Tex^(prog))and Tim-^(3+)terminally exhausted(Tex^(term))subpopulations.Inhibitor of DNA binding protein 2(Id2)has been shown to play important roles in T-cell development and CD8^(+)T-cell immunity.However,the role of Id2 in CD8^(+)T-cell exhaustion is unclear.Here,we found that Id2 transcriptionally and epigenetically regulates the generation of Texprog cells and their conversion to Texterm cells.Genetic deletion of Id2 dampens CD8^(+)T-cell-mediated immune responses and the maintenance of stem-like CD8^(+)T-cell subpopulations,suppresses PD-1 blockade and increases tumor susceptibility.Mechanistically,through its HLH domain,Id2 binds and disrupts the assembly of the Tcf3-Tal1 transcriptional regulatory complex,and thus modulates chromatin accessibility at the Slamf6 promoter by preventing the interaction of Tcf3 with the histone lysine demethylase LSD1.Therefore,Id2 increases the abundance of the permissive H3K4me2 mark on the Tcf3-occupied E-boxes in the Slamf6 promoter,modulates chromatin accessibility at the Slamf6 promoter and epigenetically regulates the generation of Slamf6+Texprog cells.An LSD1 inhibitor GSK2879552 can rescue the Id2 knockout phenotype in tumor-bearing mice.Inhibition of LSD1 increases the abundance of Slamf6^(+)Tim-3^(−)Tex^(prog) cells in tumors and the expression level of Tcf1 in Id2-deleted CD8+T cells.This study demonstrates that Id2-mediated transcriptional and epigenetic modification drives hierarchical CD8^(+)T-cell exhaustion,and the mechanistic insights gained may have implications for therapeutic intervention with tumor immune evasion.

关键词： Id2 T-cell exhaustion Epigenetic modification Immune evasion

不同形态硒及用量对幼苗期谷子生长与生理的影响

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作物杂志 2023年第1期 152-157页

作者：边淑惠邢国芳梁昕张舒玮王佳宁叶昊雨山西农业大学农学院山西太谷030800

为探究不同形态硒及用量对谷子生长和抗性的影响,选用0.0、0.1、0.5、1.0、10.0mmol/L亚硒酸钠和纳米硒,通过水培试验研究不同形态硒浓度对谷子株高、茎粗、根系、硒含量和酶活性的影响。结果表明,2种形态硒随着浓度的升高,株高均呈先... 详细信息

为探究不同形态硒及用量对谷子生长和抗性的影响,选用0.0、0.1、0.5、1.0、10.0mmol/L亚硒酸钠和纳米硒,通过水培试验研究不同形态硒浓度对谷子株高、茎粗、根系、硒含量和酶活性的影响。结果表明,2种形态硒随着浓度的升高,株高均呈先升高后降低的趋势;亚硒酸钠对茎粗的影响呈开口向下的抛物线趋势,纳米硒对茎粗有显著的抑制作用。亚硒酸钠对根长和根冠比的影响呈先增加后降低的趋势;低浓度纳米硒对根长影响不显著,高浓度纳米硒对根长有显著的抑制作用;纳米硒对谷子根冠比抑制作用明显。2种形态硒均可提高谷子的硒含量;2种形态硒及其不同浓度对超氧化物歧化酶、过氧化氢酶活性及蛋白质含量均有显著影响,对过氧化物酶活性影响不显著。结合Circos-弦图、谷子株高、茎粗、根系、硒含量和酶活性等试验结果,得出喷施0.1mmol/L的纳米硒溶液对谷子生长、硒含量及酶活性提高效果显著,适宜在谷子种植中应用。

关键词：亚硒酸钠纳米硒硒含量酶活性谷子

Plant genomic resources at National Genomics Data Center:assisting in data-driven breeding applications

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aBIOTECH 2024年第1期5卷 94-106页

作者： Dongmei Tian Tianyi Xu Hailong Kang Hong Luo Yanqing Wang Meili Chen Rujiao Li Lina Ma Zhonghuang Wang Lili Hao Bixia Tang Dong Zou Jingfa Xiao Wenming Zhao Yiming Bao Zhang Zhang shuhui Song National Genomics Data Center Beijing Institute of GenomicsChinese Academy of Sciences&China National Center for BioinformationBeijing 100101China CAS Key Laboratory of Genome Sciences and Information Beijing Institute of GenomicsChinese Academy of Sciences&China National Center for BioinformationBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Genomic data serve as an invaluable resource for unraveling the intricacies of the higher plant systems,including the constituent elements within and among species.Through various efforts in genomic data archiving,integrative analysis and value-added curation,the National Genomics Data Center(NGDC),which is a part of the China National Center for Bioinformation(CNCB),has successfully established and currently maintains a vast amount of database resources.This dedicated initiative of the NGDC facilitates a data-rich ecosystem that greatly strengthens and supports genomic research efforts.Here,we present a comprehensive overview of central repositories dedicated to archiving,presenting,and sharing plant omics data,introduce knowledgebases focused on variants or gene-based functional insights,highlight species-specific multiple omics database resources,and briefly review the online application tools.We intend that this review can be used as a guide map for plant researchers wishing to select effective data resources from the NGDC for their specific areas of study.

关键词： Plant-omics data Data repositories Data integration Knowledgebase Plant genomics

CRL2^(APPBP2)-mediated TSPYL2 degradation counteracts human mesenchymal stem cell senescence

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Science China(Life Sciences) 2024年第3期67卷 460-474页

作者： Daoyuan Huang Qian Zhao Kuan Yang Jinghui Lei Ying Jing Hongyu Li Chen Zhang Shuai Ma shuhui Sun Yusheng Cai Guibin Wang Jing Qu Weiqi Zhang Si Wang Guang-Hui Liu Advanced Innovation Centerfor Human Brain Protection National Clinical Research Centerfor Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational MedicineCenter International Centerfor Aging and CancerBejing Municipal GeriatricMedical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Beijing Institute for Stem Cell and Regenerative Medicine Beijing100101China CAS Key Laboratory of Genomic and Precision Medicine Bejing Institute of Genomics and China National Center for BioinformationChinese Academy of SciencesBeijing 100101China Institute for Stem Cell and Regeneration CASBeijing 100101China The Fifth People's Hospital of Chongqing Chongqing 400062China Sino-Danish Cllege University of Chinese Academy of SciencesBeijing101408China National Laboratory of Biomacromolecules CAS Center for Excelence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing100101China State Key Laboratory of Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijing 102206China

Cullin-RING E3 ubiquitin ligases(CRLs),the largest family of multi-subunit E3 ubiquitin ligases in eukaryotic cells,represent core cellular machinery for executing protein degradation and maintaining proteostasis.Here,we asked what roles Cullin proteins play in human mesenchymal stem cell(hMSC)homeostasis and senescence.To this end,we conducted a comparative aging phenotype analysis by individually knocking down Cullin members in three senescence models:replicative senescent hMSCs,Hutchinson-Gilford Progeria Syndrome hMSCs,and Werner syndrome hMSCs.Among all family members,we found that CUL2 deficiency rendered hMSCs the most susceptible to senescence.To investigate CUL2-specific underlying mechanisms,we then applied CRISPR/Cas9-mediated gene editing technology to generate CUL2-deficient human embryonic stem cells(hESCs).When we differentiated these into h MSCs,we found that CUL2 deletion markedly accelerates hMSC senescence.Importantly,we identified that CUL2 targets and promotes ubiquitin proteasome-mediated degradation of TSPYL2(a known negative regulator of proliferation)through the substrate receptor protein APPBP2,which in turn downregulates one of the canonical aging marker-P21^(waf1/cip1),and thereby delays senescence.Our work provides important insights into how CRL2^(APPBP2)-mediated TSPYL2 degradation counteracts hMSC senescence,providing a molecular basis for directing intervention strategies against aging and aging-related diseases.

关键词： Cullins stem cell senescence aging proteostasis ubiquitination APPBP2 TSPYL2

体育电商直播女性观众的个人特征与居住环境对在线体育消费的综合影响

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武汉体育学院学报 2024年第5期58卷 51-58页

作者：黄颖孙淑慧成都体育学院体育学博士后科研流动站四川成都610041 成都体育学院外国语学院四川成都610041 成都体育学院学术期刊中心四川成都610041

研究探索了体育电商直播中女性观众的个人特质与居住环境对其在线体育消费行为的综合影响。通过问卷调查与数据分析,研究发现职位职级、收入水平、婚姻状况以及居住地的空气质量(具体为二氧化硫年平均浓度)对女性观众的在线消费行为产... 详细信息

研究探索了体育电商直播中女性观众的个人特质与居住环境对其在线体育消费行为的综合影响。通过问卷调查与数据分析,研究发现职位职级、收入水平、婚姻状况以及居住地的空气质量(具体为二氧化硫年平均浓度)对女性观众的在线消费行为产生了显著影响。第一,身处高层职位、收入中等以及已婚的女性更倾向于在体育电商直播平台进行消费。这验证了社会阶层和生命周期背景对女性观众的在线体育消费决策具有重要影响。第二,当居住城市的空气质量恶化时,女性观众在体育电商直播平台上的消费意愿会相应增加,这暗示着环境因素与个体特征之间可能存在着某种协同作用。第三,粉丝身份进一步推动了女性观众的在线体育消费行为。这表明,在制定营销策略时,必须充分考虑粉丝身份及其背后的心理需求与行为模式。这些发现不仅为政策制定提供了启示,还为体育电商直播平台制定个性化推广策略、提供精准服务提供了重要的参考依据。

关键词：体育电商直播女性个人特征居住环境在线体育消费